MthK is a prokaryotic Ca2+-gated K+ channel that, like other ligand-gated channels, converts the chemical energy of ligand binding to the mechanical force of channel opening. The channel's eight ligand-binding domains, the RCK domains, form an octameric gating ring in which Ca2+ binding induces conformational changes that open the channel. Here we present the crystal structures of the MthK gating ring in closed and partially open states at 2.8 Å, both obtained from the same crystal grown in the absence of Ca2+. Furthermore, our biochemical and electrophysiological analyses demonstrate that MthK is regulated by both Ca2+ and pH. Ca2+ regulates the channel by changing the equilibrium of the gating ring between closed and open states, while pH regulates channel gating by affecting gating-ring stability. Our findings, along with the previously determined open MthK structure, allow us to elucidate the ligand gating mechanism of RCK-regulated K+ channels.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)